Abstract The focus of the active parent grant (Long-term Benefits & Harms of Antihypertensive Drugs in the Elderly: Up to 22-year Follow-Up of ALLHAT Trial Participants) is to determine if there are any long-term benefits for the reduced risk of coronary heart disease (CHD), cardiovascular disease (CVD), stroke, and mortality in those receiving diuretics as compared to those receiving other antihypertensive drugs into next 15-year post-trial surveillance period after taking into consideration post-trial antihypertensive medication usage from Medicare Part-D pharmacy data; and if long-term side effects, such as cancer and depression which are identifiable from post-marketing surveillance of Medicare claims, are similar among the 3 arms of antihypertensive drugs. The goal will be achieved by linking the data of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) participants with their Medicare data up to 2017, making the total follow-up time up to 23 years (including 8-year in-trial and 15-year post-trial follow-up). Antihypertensive drug therapies have recently been associated with a lower risk of developing dementia and early cognitive impairment. For example, in 2019 the Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (MIND) study reported that intensive blood pressure (BP) control significantly reduced the risk of mild cognitive impairment. This was the first trial to demonstrate an effective strategy for the prevention of age-related cognitive impairment. Given a high prevalence of hypertension in adult population, adequate utilization of disease- modifying drugs may provide an effective strategy for prevention of Alzheimer?s disease (AD) and related dementias (ADRD). However, there is no large and long-term follow-up study monitoring and assessing the effects of antihypertensive medications on the risk of ADRD. Therefore, with the detailed blood pressure control data available during the trial follow-up in ALLHAT participants and with the data of those participants linked with their Medicare Part-D drug data up to 2017, we will be able to determine whether blood pressure control and antihypertensive drugs are associated with the decreased risk of ADRD during the 23 years of follow-up from 1994 to 2017. We will address the following specific aims in this Alzheimers-focused Administrative Supplement: 1) to determine the risk of ADRD in association with blood pressure control and antihypertensive treatments (diuretics, ACE inhibitors, and calcium channel blockers) in ALLHAT participants; and 2) to examine whether and to what extent the post-trial antihypertensive medication usage from Medicare Part-D data affect the risk of ADRD in ALLHAT participants with 3 trial treatment arms (diuretics, ACE inhibitors, and calcium channel blockers), while taking into consideration death as a competing risk and adjusting for comorbid conditions and other confounders.